The finding of CRH-R2 in cardiac tissue leads to the hypothesis tested in this proposal: cardiac-specific responses to CRH occur via CRH receptors localized in the heart. The primary prediction is that certain specific cardiac effects of CRH occur through CRH-R2. The source of CRH that acts on the cardiac CRH-R2 may be via local synthesis in the heart and /or from production in the central nervous system. The aims are: Aim 1: Determine which cells in the mouse heart express CRH receptors. Aim 2: To examine the interaction of two peptide ligands, CRH and urocortin, with the CRH-R2 receptor and to determine the second messenger systems to which the receptor is coupled. Aim 3: Determine the mechanism(s) involved in cardiac CRH-R2 regulation by the stress-related stimulus, bacterial endotoxin.